The main interest of our laboratory is the immune response to tumors, primarily using murine models. We are currently studying the B-16 melanoma tumor system where a tumor-associated antigen, GP-l00, was recently identified in the Surgery Branch. We are now investigating a variety of ways to immunize against GP-100 in order to both prevent and treat established B-16 melanoma. These include recombinant viral approaches as well as attempts to identify a peptide epitope and direct peptide immunization. Similar efforts are on-going to establish whether the MART-1 murine homolog also serves as a tumor rejection antigen for B- 16 melanoma. Other laboratory efforts are studying the use of an altered beta chain of the murine class II MHC molecule, covalently modified to carry the epitope for a model antigen, sperm whale myoglobin (SWM). This is being utilized to investigate the role of CD4+ cells and class II antigen presentation in tumor rejection using a murine tumor transduced with SWM. The modified beta chain has been constructed and functions in vitro, and current efforts are directed at utilizing this and vaccination strategies in vivo. Clinically, the major efforts continue to be a randomized trial comparing three alternate interleukin-2 regimens for the treatment of metastatic renal cell cancer. Over 200 patients are randomized in this trial, and it continues at present. In the area of adult soft tissue sarcoma, two randomized trials continue investigating the use of adjuvant chemotherapy for high-grade extremity sarcoma and adjuvant radiotherapy for low-grade sarcoma at all sites.